Cooperative heterometallic platforms enabling selective C–H bond activation and functionalization of pyridines

The development of methodologies for regioselective C–H functionalization of N-heterocycles has seen sustained growth over the last two decades. Cooperative reactivity stemming from the addition of Lewis-acidic metals to late-transition-metal complexes has enabled regioselective catalytic transformations. Progress in the design of ligands and Lewis-acidic metal precursors has led to development of in situ cooperative catalysts able to facilitate C–H functionalization of pyridine at C-2, C-3, and C-4 positions. Very recently, focused efforts toward well-defined heterometallic complexes facilitating C-H bond catalysis have been targeted. Transformations showcasing regioselective C-2 transformations have been achieved. This perspective examines select examples delineating the evolution of strategies to better facilitate cooperative reactivity between Lewis-acidic metals and late transition metals in regioselective C–H functionalization. Potential pathways to further evolve methods to access modular regiodivergence in pyridine C–H bond catalysis will be discussed

Mount Elgon\u27s Elephants Are in Peril

The elephants at Mount Elgon National Park (MENP) are unique and exceptional. They are the only elephants known to excavate for salt in underground caves. Data on the ecology of elephants at MENP were collected over a period of seven years with a total of 130 days of field observations. Methods employed included: direct observations, spoor, photographs, and sound recording. Elephants visited the caves singly or in groups of up to 19 individuals; visits lasted up to 6 hours in Kitum and Makingeny Caves. Most visits began around dusk, but occasionally they entered in daytime or later at night. The frequency of visits by elephants to the caves seemed to increase as the rainfall decreased. Also observed at the caves were bats, ungulates, monkeys, rodents, carnivores, birds, and insects. Plants, rocks, and water samples are being analyzed. It appears that the formation of these caves resulted from the combined efforts of salt mining and/or eating activities over millions of years by elephants and other animals and also by pastoral African tribes. In the early 1970\u27s the elephant population in MENP was estimated to be 1,200 ± 100; today perhaps only 50-130 are left. This decline of 10- to 26-fold is mostly due to ivory poaching, which increased dramatically since 1986. If this trend continues, Mount Elgon\u27s already depleted elephant population will become extinct. This would also mean the end of the unprecedented mining behavior - a potential tourist attraction comparable to Rwanda\u27s mountain gorillas in its appeal to tourists. Recommendations and proposals for action include publicity and fund-raising in order to better equip and enlarge anti-poacher patrols, to encourage controlled tourism, and to define research and conservation work related to Mount Elgon\u27s ecosystem

Ligand architecture for triangular metal complexes: a high oxidation state Ni₃ cluster with proximal metal arrangement

A new multidentate tetraanionic ligand platform for supporting trinuclear transition metal clusters has been developed. Two trisphenoxide phosphinimide ligands bind three Ni centers in a triangular arrangement. The phosphinimide donors bridge in µ₃ fashion and the phenoxides complete a pseudo-square planar coordination sphere around each metal center. Electrochemical studies reveal two pseudo-reversible oxidation events at notably low potentials (−0.80 V and +0.05 V). The one electron oxidized species was characterized structurally, and it is assigned as a Ni^(III)-containing cluster

The polarized expression of Na+,K+-ATPase in epithelia depends on the association between beta-subunits located in neighboring cells

The polarized distribution of Na+,K+-ATPase plays a paramount physiological role, because either directly or through coupling with co- and countertransporters, it is responsible for the net movement of, for example, glucose, amino acids, Ca2+, K+, Cl-, and CO3H- across the whole epithelium. We report here that the beta-subunit is a key factor in the polarized distribution of this enzyme. 1) Madin-Darby canine kidney (MDCK) cells (epithelial from dog kidney) express the Na+,K+-ATPase over the lateral side, but not on the basal and apical domains, as if the contact with a neighboring cell were crucial for the specific membrane location of this enzyme. 2) MDCK cells cocultured with other epithelial types (derived from human, cat, dog, pig, monkey, rabbit, mouse, hamster, and rat) express the enzyme in all (100%) homotypic MDCK/MDCK borders but rarely in heterotypic ones. 3) Although MDCK cells never express Na+,K+-ATPase at contacts with Chinese hamster ovary (CHO) cells, they do when CHO cells are transfected with beta(1)-subunit from the dog kidney (CHO-beta). 4) This may be attributed to the adhesive property of the beta(1)-subunit, because an aggregation assay using CHO (mock-transfected) and CHO-beta cells shows that the expression of dog beta(1)-subunit in the plasma membrane does increase adhesiveness. 5) This adhesiveness does not involve adherens or tight junctions. 6) Transfection of beta(1)-subunit forces CHO-beta cells to coexpress endogenous a-subunit. Together, our results indicate that MDCK cells express Na+,K+-ATPase at a given border provided the contacting cell expresses the dog P,-subunit. The cell-cell interaction thus established would suffice to account for the polarized expression and positioning of Na+,K+-ATPase in epithelial cells

Ahmed , The Logo of the Elephant Interest Group: Encounters in Marsabit and Notes on His Model and Skeleton

Ahmed , the logo of the Elephant Interest Group, was a male African elephant (Loxodonta africana) that was born about 1919, possibly in the vicinity of Marsabit National Reserve, Kenya, East Africa. The name Ahmed is of Arabic origin (pronounced Ah-med ), and it means praised. At the age of 55 Ahmed was about 3 m (10 ft) tall at the shoulder and weighed approximately 5 metric tons (about 11,000 lbs.). He had huge tusks for his size, measuring about 3 m (10 ft) each and averaging about 70 kg (150 lbs) each. Ahmed\u27s 300 pounds of ivory attracted hunters and, as a result, raised major concern for his safety among scientists and the general public. A total of 5,000 letters and cards was delivered to the East African Wildlife Society and resulted in a Presidential Decree issued by the late President Mzee Jomo Kenyatta to protect Ahmed. In addition, a team of human soldiers was assigned to watch his whereabouts around the clock. On January 17, 1974 Ahmed died, probably of natural causes, and his carcass was found almost two days later near Lake Paradise, in the Reserve. The skin was already in an advanced stage of decomposition. Ahmed was dissected on the spot by a team from the Zimmermann (1973) Limited Taxidermist, headed by Wolfgang Schenk, and the skeleton was transported to Nairobi, the capital, where it was prepared and mounted by J.C. Hillman. A fiberglas replica of the skin was made by Zimmermann\u27s team. The entire operation lasted two years and cost Kenyan Shillings 143,086 (about US $14,500). Both the skeleton and the replica are now on display at the National Museum of Kenya (NMK) in Nairobi. Ahmed is Kenya\u27s most celebrated elephant; he was and still is regarded as a national monument and remains the symbol of conservation. The NMK and the Kenyan Government should be commended for their tremendous efforts in preserving the remains of Ahmed

Proboscidean DNA from Museum and Fossil Specimens: An Assessment of Ancient DNA Extraction and Amplification Techniques

Applications of reliable DNA extraction and amplification techniques to postmortem samples are critical to ancient DNA research. Commonly used methods for isolating DNA from ancient material were tested and compared using both soft tissue and bones from fossil and contemporary museum proboscideans. DNAs isolated using three principal methods served as templates in subsequent PCR amplifications, and the PCR products were directly sequenced. Authentication of the ancient origin of obtained nucleotide sequences was established by demonstrating reproducibility under a blind testing system and by phylogenetic analysis. Our results indicate that ancient samples may respond differently to extraction buffers or purification procedures, and no single method was universally successful. A CTAB buffer method, modified from plant DNA extraction protocols, was found to have the highest success rate. Nested PCR was shown to be a reliable approach to amplify ancient DNA templates that failed in primary amplification.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44162/1/10528_2004_Article_413527.pd

Frameshift Mutagenesis and Microsatellite Instability Induced by Human Alkyladenine DNA Glycosylase

Human alkyladenine DNA glycosylase (hAAG) excises alkylated purines, hypoxanthine, and etheno bases from DNA to form abasic (AP) sites. Surprisingly, elevated expression of hAAG increases spontaneous frameshift mutagenesis. By random mutagenesis of eight active site residues, we isolated hAAG-Y127I/H136L double mutant that induces even higher rates of frameshift mutation than does the wild-type hAAG; the Y127I mutation accounts for the majority of the hAAG-Y127I/H136L-induced mutator phenotype. The hAAG-Y127I/H136L and hAAG-Y127I mutants increased the rate of spontaneous frameshifts by up to 120-fold in S. cerevisiae and also induced high rates of microsatellite instability (MSI) in human cells. hAAG and its mutants bind DNA containing one and two base-pair loops with significant affinity, thus shielding them from mismatch repair; the strength of such binding correlates with their ability to induce the mutator phenotype. This study provides important insights into the mechanism of hAAG-induced genomic instability.National Institutes of Health (U.S.) (Grant CA055042)National Institutes of Health (U.S.) (Grant CA115802)National Institutes of Health (U.S.) (Grant ES02109